Rituximab-Related Osteonecrosis Of The Jaw In A Patient Presenting With B Cell Lymphoma

OBJECTIVESWe report a case of a patient presented with a suspect gingival swelling who is been diagnosed with B cell lymphoma and has developed, subsequently to the treatment for the neoplasia (including rituximab associated to high dose corticosteroids), a medication related osteonecrosis of the maxilla.MATERIALS AND METHODSA 71-year-old patient came to our attention presenting, at the intraoral objective examination, a swelling of the adherent gingiva of the upper anterior segment (II sextant), both vestibular and palatal, of diminuished consistency and slightly lighter color than the physiological counterpart. The lesion was not painful at palpation and extended from the vestibular archway to cover about half of the crowns of the upper central incisors. Beneath the superficial epithelial layers a rich vascularization was evident. Following the biopsy sampling of the gingival neoformation, an anatomopathologic diagnosis of NHL, diffuse large B-cell lymphoma was posed. The patient underwent immunochemotherapy according to the R-CHOP scheme - rituximab 1400 mg, cyclophosphamide 1500 mg, doxorubicin (Adriblastina (R)) 80 mg, vincristine (Oncovin (R)) 2 mg - associated with methylprednisolone 80 mg. After the third cycle of immunochemotherapy, he developed a bone exposition of the anterior maxilla, compatible at clinical diagnosis with a picture of medication related osteonecrosis (MRONJ), which was further investigated by incisional biopsy and treated with antibiotics and sequestrectomy. The lesion was treated by antibiotic therapy and sequestrectomy of the necrotic bone portion and with simultaneous biopsy of the same.RESULTS AND CONCLUSIONSThe histological examination confirmed the first hypothesis of medication-related osteonecrosis of the maxilla, correlated to the treatment with rituximab and steroids, as prescribed following the scheme of immunochemotherapy: R-rituximab, C-cyclophosphamide, H-doxorubicin (hydroxydaunomycin), O-vincristine, P-prednisolone (R-CHOP). The treatment of these lymphoproliferative diseases is traditionally based on chemotherapy, radiotherapy and bone marrow transplantation. Recently, monoclonal antibodies, including rituximab, have been introduced with excellent results, as an aid in the treatment of these diseases. In fact, B-cell lymphomas are highly expressive of specific surface proteins such as CD19, CD20, and CD22, that represent potential therapeutic targets. CD20 is particularly involved in the regulation of intracellular calcium, cell cycle and apoptotic mechanisms. Rituximab is a monoclonal anti-CD20 antibody, defined as a chimeric type since it has a percentage of murine amino acids (equal to about 34% of the total), while the remaining part is of human origin. Recognizing the CD20 antigen expressed in tumor B cells, rituximab leads to apoptosis of the same by various mechanisms including complement cascade activation, apoptosis-related signaling induction, and antibody-mediated direct cytotoxicity. As with other biological agents used, the use of rituximab has potential adverse effects. About one in three cases shows infusion reactions that are not life-threatening (nausea, hypertension, pruritus, chills, rigidity, etc.) while infections affect 39% of patients treated with this drug. In recent years, an increasing number of studies reported cases of avascular osteonecrosis of the jaws drug-correlated (medication-related osteonecrosis of the jaws, MRONJ), among these medication also monoclonal antibodies are found.CLINICAL SIGNIFICANCEBased on the growing number of cases, many different categories of drugs seem associated with the onset of osteonecrosis of the maxillary bones. It is therefore necessary to recognize the concrete possibility of the onset of bone necrosis even in patients not in therapy with anti-bone resorption or anti-angiogenetic drugs.